investigational treatment of Parkinson's disease
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Notes
- transplants of adrenal medullary & fetal tissue into the striatum[4]
- grafted cells reinnervate large swaths of the striatum into which they were implanted
- grafted cells survive for more than 1 decade
- symptoms may improve for as long as 1 decade
- grafted cells develop neuropathologic features of Parkinson disease over time (Lewy bodies)[5]
- neuroimmunophilins
- glial cell-derived neurotrophic factor (GDNF)
- neotrofin
- epidural electrodes over the motor cortex improves bradykinesia in primates[2]
- adenosine-A2A-receptor antagonists may be of benefit for motor fluctuations (investigational)
- squalamine phosphate (ENT-01) may improve constipation & cognition in patients with Parkinson's disease[10]
- gene therapy
- injection of viral vector (lentivirus) into the putamen
- AADC gene therapy[7]
- sirtuin-2 inhibitors rescue alpha-synuclein-mediated toxicity in fruit fly model of Parkinson's disease[3]
- dihydropyridine calcium-channel blocker isradipine does not slow progression of disease[8]
- simvastatin of no benefit as Parkinson's disease-modifying agent[9]
- brain iron chelation with deferiprone associated with worsening of parkinsonism symptoms & adverse events in early Parkinson's disease[11]
- foscarbidopa/foslevodopa by continuous subcutaneous infusion may increase "on" time without increasing dyskinesia[12]
More general terms
References
- ↑ Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 2.0 2.1 Journal Watch 25(1):11, 2005 Drouot X, Oshino S, Jarraya B, Besret L, Kishima H, Remy P, Dauguet J, Lefaucheur JP, Dolle F, Conde F, Bottlaender M, Peschanski M, Keravel Y, Hantraye P, Palfi S. Functional recovery in a primate model of Parkinson's disease following motor cortex stimulation. Neuron. 2004 Dec 2;44(5):769-78. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15572109
- ↑ 3.0 3.1 Outeiro TF et al, Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 2007, 317:516
- ↑ 4.0 4.1 Freed CR et al Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001; 344:710 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11236774
- ↑ 5.0 5.1 Kordower JH et al Transplanted dopaminergic neurons develop PD pathologic changes: A second case report. Mov Disord 2008 Dec 15; 23:2303. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19006193
Li JY etl al Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008; 14:501 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18391963
Kordower JH Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 2008; 14:504 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18391962 - ↑ 6.0 6.1 Palfi S et al Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412048 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961939-X/abstract
Stoessl AJ Gene therapy for Parkinson's disease: a step closer? The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412047 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962108-X/fulltext - ↑ 7.0 7.1 Christine CW, Bankiewicz KS, Van Laar AD et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease. Ann Neurol. 2019 May;85(5):704-714. Epub 2019 Mar 26. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30802998 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25450
Christine CW, Richardson RM, Van Laar AD et al. Safety of AADC gene therapy for moderately advanced Parkinson disease: Three-year outcomes from the PD-1101 trial. Neurology 2021 Oct 14; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34649873 https://n.neurology.org/content/early/2021/10/14/WNL.0000000000012952 - ↑ 8.0 8.1 The Parkinson Study Group STEADY-PD III Investigators. Isradipine versus placebo in early Parkinson disease: A randomized trial. Ann Intern Med 2020 Mar 31; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32227247 https://annals.org/aim/article-abstract/2763874/isradipine-versus-placebo-early-parkinson-disease-randomized-trial
- ↑ 9.0 9.1 Stevens KN, Creanor S, Jeffery A et al Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease. A Randomized Clinical Trial. JAMA Neurol. Published online October 31, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36315128 https://jamanetwork.com/journals/jamaneurology/fullarticle/2797508
- ↑ 10.0 10.1 Camilleri M et al. Oral ENT-01 targets enteric neurons to treat constipation in Parkinson disease: A randomized controlled trial. Ann Intern Med 2022 Nov 8; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36343348 https://www.acpjournals.org/doi/10.7326/M22-1438
- ↑ 11.0 11.1 George J Brain Iron Chelation Linked With Worse Outcomes in Early Parkinson's. Findings raise caution about iron chelation in neurodegenerative disorders. MedPage Today December 2, 2022 https://www.medpagetoday.com/neurology/parkinsonsdisease/102035
Devos D, Labreuche J, Rascol O et al Trial of Deferiprone in Parkinson's Disease. N Engl J Med 2022; 387:2045-2055. Dec 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36449420 https://www.nejm.org/doi/full/10.1056/NEJMoa2209254 - ↑ 12.0 12.1 Rosebraugh M et al. Foslevodopa/foscarbidopa: A new subcutaneous treatment for Parkinson's disease. Ann Neurol 2021 Mar 26; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33772855 https://onlinelibrary.wiley.com/doi/10.1002/ana.26073
Soileau MJ et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: A randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol 2022 Dec; 21:1099 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36402160 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00400-8/fulltext